Fig. 1

Epigenetic modifier proteins control cognition and behavior. An illustration summarizing the broad categories of epigenetic mechanisms that are disrupted in select MDEMs. Specifically highlighted are the mechanisms and conditions described in detail in this review. Mutations in epigenetic protein modifiers—DNA methylation writers (green marker), erasers (pink eraser), readers (glasses), and chromatin remodelers (truck)—drive atypical cognitive and behavioral development in MDEMs. Specifically, loss of function in different components of epigenetic machinery results in unique neurodevelopmental disorders. Variants in DNMT3A (a writer) affect DNA methylation causing Tatton Brown Rahman syndrome. Variants in TET3 (an eraser) affect DNA demethylation causing Beck Fahrner syndrome. Variants in CHD7 (a remodeler) impact chromatin remodeling causing CHARGE syndrome. Variants in CREBBP/EP300 and KAT6A (primary writers with a reader component) result in histone acetylation dysregulation causing Rubinstein Taybi syndrome and KAT6A syndrome, respectively. Variants in KMT2D (primary writer with reader component)/KDM6A (eraser) and KMT2A (primary writer with reader component) dysregulate histone methylation causing Kabuki syndrome and Wiedemann-Steiner syndrome, respectively